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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Neurol. Mar 28, 2015; 5(1): 5-16
Published online Mar 28, 2015. doi: 10.5316/wjn.v5.i1.5
Targeting remyelination treatment for multiple sclerosis
Maheen Nadeem, Lindsay Sklover, Jacob A Sloane
Maheen Nadeem, Lindsay Sklover, Jacob A Sloane, Multiple Sclerosis Center, Beth Israel Deaconess Medical Center, Boston, MA 02115, United States
Author contributions: All authors contributed to this work.
Conflict-of-interest: There is no conflict of interest on the part of any author of this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jacob A Sloane, Director, Multiple Sclerosis Center, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Ks212, Boston, MA 02115, United States. jsloane@bidmc.harvard.edu
Telephone: +1-617-6673742 Fax: +1-617-6671869
Received: September 28, 2014
Peer-review started: September 29, 2014
First decision: October 21, 2014
Revised: December 9, 2014
Accepted: December 18, 2014
Article in press: December 19, 2014
Published online: March 28, 2015
Processing time: 236 Days and 17.2 Hours
Abstract

Since disability in multiple sclerosis (MS) is a product of neurodegeneration and deficient remyelination, the ability to enhance neuroregeneration and myelin regeneration in MS is an enticing goal for MS drug development. In particular, remyelination treatments could promote return of neurological function and also prevent further axonal loss and neurodegeneration in MS due to trophic effects of myelin. The study of remyelination has advanced dramatically in the last several years such that a number of pathways inhibiting remyelination have been discovered, including those involving LINGO-1, Notch-1, hyaluronan, retinoid X receptor, and wnt/ß-catenin. Other approaches such as high throughput drug screening for remyelination drugs have caught fire, with identification of dozens of known drugs with oligodendrocyte maturation stimulatory effects. Several drugs identified through screens and other mechanisms are in the process of being further evaluated for remyelination in MS and MS models. We discuss the potential molecular targets and the variety of mechanisms towards drug identification and development in remyelination for MS.

Keywords: Multiple sclerosis; Myelin; Remyelination; Oligodendrocyte; Repurposing; Treatment

Core tip: Over the last several years numerous remyelination pathways important to multiple sclerosis (MS) have been identified, including those of LINGO-1, hyaluronan, Notch-1, retinoid X receptor receptor, and wnt/ß-catenin. Newer discoveries include the pathways involving Chemokine (C-X-C Motif) ligand 12/C-X-C chemokine receptor type 4 and G protein-coupled receptor 17, and the involvement of Endothelin-1 in the Notch pathway. High-throughput screens have identified multiple antimuscarinic drugs with good remyelination. Also identified by screens, clemastine, with similar antimuscarinic but also antihistamine effects, may be useful in remyelination in MS. Drug repurposing, through screens or more serendipitously, has found that many drugs could enhance remyelination, including benztropine, clemastine, quetiapine, fasudil, olesoxime, and ibudilast, among others.